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PubMed2006

Repair of skin damage during fractionated irradiation with gamma rays and low-LET carbon ions.

In clinical use of carbon-ion beams, a deep-seated tumor is irradiated with a Spread-Out Bragg peak (SOBP) with a high-LET feature, whereas surface skin is irradiated with an entrance plateau, the LET of which is lower than that of the peak. The repair kinetics of murine skin damage caused by an entrance plateau of carbon ions was compared with that caused by photons using a scheme of daily fractionated doses followed by a top-up dose. Right hind legs received local irradiations with either 20 keV/microm carbon ions or gamma rays. The skin reaction of the irradiated legs was scored every other day up to Day 35 using a scoring scale that consisted of 10 steps, ranging from 0.5 to 5.0. An isoeffect dose to produce a skin reaction score of 3.0 was used to obtain a total dose and a top-up dose for each fractionation. Dependence on a preceding dose and on the time interval of a top-up dose was examined using gamma rays. For fractionated gamma rays, the total dose linearly increased while the top-up dose linearly decreased with an increase in the number of fractions. The magnitude of damage repair depended on the size of dose per fraction, and was larger for 5.2 Gy than 12.5 Gy. The total dose of carbon ions with 5.2 Gy per fraction did not change till 2 fractions, but abruptly increased at the 3rd fraction. Factors such as rapid repopulation, induced repair and cell cycle synchronization are possible explanations for the abrupt increase. As an abrupt increase/decrease of normal tissue damage could be caused by changing the number of fractions in carbon-ion radiotherapy, we conclude that, unlike photon therapy, skin damage should be carefully studied when the number of fractions is changed in new clinical trials.

Animals↗
PubMed2001

Processing of the insulin-like growth factor-II-mannose 6-phosphate receptor in isolated liver subcellular fractions.

A truncated, soluble form of the insulin-like growth factor-II-mannose 6-phosphate (IGF-II-M6P) receptor has been identified in serum and shown to be released from cultured tissues and cells, liver being the main contributor to serum receptor in adult rats. In the present study, the processing of the IGF-II-M6P receptor has been characterized in isolated liver subcellular fractions using ligand binding, affinity crosslinking, and Western immunoblotting techniques. The receptor in plasma membrane fractions differed from that in Golgi-endosomal fractions by: (i) a lower molecular size upon reducing polyacrylamide gel electrophoresis (245 vs. 255 kDa); (ii) a less tight membrane association as judged upon extractibility by NaCI; and (iii) the inability to recognize antibody anti-22C, directed against the cytoplasmic domain of the receptor. Incubation of cell fractions at 30 degrees C led to a pH- and time-dependent release of the receptor into the medium. The pH optimum for release was 5.5 in the Golgi-endosomal fraction and 7.5 in plasma membrane fractions; at this pH, approximately 2% and 20%-30% of total receptors were released per hour, respectively. Receptor release was inhibited in a dose-dependent manner by aprotinin, benzamidine, and leupeptin in the Golgi-endosomal fraction, and by 1,10 phenanthroline in plasma membrane fractions, although high concentrations were required for inhibition. The receptor released from Golgi-endosomes showed a 5-10 kDa reduction in size and a loss of ability to recognize antibody anti-22C, but that released from plasma membranes showed little or no changes in size. We conclude that soluble, carboxy-terminally truncated forms of the IGF-II-M6P receptor are generated from the intact receptor in isolated Golgi-endosomal and plasma membrane fractions. However, receptor processing in these fractions exhibits different properties, suggesting the involvement of different proteases.

Animals↗
PubMed1986

High resolution of heterogeneity among human neutrophil granules: physical, biochemical, and ultrastructural properties of isolated fractions.

Previous studies on the fractionation of human neutrophil granules have identified two major populations: myeloperoxidase (MPO)-containing azurophil, or primary, granules and MPO-deficient specific, or secondary, granules. Peripheral blood neutrophils from individual donors were lysed in sucrose-free media by either hypotonic shock or nitrogen cavitation. Using a novel two-gradient Percoll density centrifugation system, the granule-rich postnuclear supernatant was rapidly (ten minutes) and reproducibly resolved into 13 granule fractions (L1 through L8 and H1 through H5). Granule flotation and recentrifugation experiments on both continuous, self-generated and multiple-step gradients using individual and mixed isolated fractions demonstrated that the banding patterns were isopycnic and nonartifactual. Isolated granules were intact based on the findings that biochemical latency of several granule enzymes was greater than 95%, and thin-sectioned electron micrographs demonstrated intact granule profiles. Biochemical analyses of the granule marker proteins MPO, beta-glucuronidase, lysozyme, and lactoferrin indicated that a number of the fractions were related to the major azurophil and specific granule populations. Lactoferrin was found in ten of 13 fractions (L1 through L8, H1 to H2), whereas MPO was found in every fraction. Consistent with these biochemical data, all fractions exhibited varying degrees of heterogeneity based on ultrastructural morphology and cytochemistry, including diaminobenzidine (DAB) reactivity for peroxidase and periodate-thiocarbohydrazide-silver proteinate (PA-TCH-SP) staining for complex glycoconjugates. A variable but significant percentage (23% to 70%) of the granules in fractions L1 through L8 and H1 and H2 showed DAB reactivity, while about 90% of the granules in fractions H3 through H5 were peroxidase positive. These results demonstrated that DAB-reactive granules spanned the entire range of granule size and density. Ultrastructural PA-TCH-SP staining of isolated granule fractions revealed patterns similar to those of granules in intact neutrophils at different stages of development. Granules from human acute promyelocytic leukemia cells (HL-60) exhibited a surprisingly low density compared with typical azurophil granules from normal, mature neutrophils. The data suggest that both functional and maturational differences contribute to granule heterogeneity, and provide a new practical and conceptual framework for further defining the phenomenon of neutrophil granule heterogeneity.

Cell Fractionation↗
PubMed1981

Reduced antitumor and immune-adjuvant activities of the sub-cellular fractions from Group A Streptococcus.

The sub-cellular fractions from Group A streptococcus (Su-strain) were prepared, and their antitumor and biological activities were examined. The cell wall fraction (CWF) and the protoplast membrane fraction (PMF) were slightly effective in retarding the growth of Ehrlich ascites carcinoma in outbred ddY mice when either fraction was used in combination with 5-FU. The cytoplasmic particle fraction (CPF) and the cytoplasmic soluble fraction (CSF), however, were not effective. In the B6D2F1 mice-L 1210 leukemia system, none of the subcellular fractions were beneficial even when combined with 5-FU. Further, the antitumor effect of OK-432 was completely abolished by disruption of the preparation, indicating that antitumor activity of OK-432 may depend on the structural integrity of the cocci in the preparation. Despite the general lack of anti-tumor activity in the mouse systems, the subcellular fractions, including those of OK-432, inhibited the growth of Yoshida sarcoma cells in culture and the uptake of [2H]-UR and [3H]-TdR by L 1210 cells in vitro. The immunopotentiating activities of these fractions, however, were demonstrated to be markedly diminished as compared with those of OK-432 and heated Su-cocci (60 degrees C, 30 min). The present study, therefore, shows that the decreased antitumor activity of the subcellular fractions closely correlate to the decrease of their immunopotentiating activities.

Adjuvants, Immunologic↗
PubMed1994

[Analysis of Fas antigen gene expression in human thymocytes fractionated with discontinuous gradients using bovine serum albumin].

Premature thymocytes proliferate and differentiate from immature to mature T lymphocytes through out both positive and negative selections in thymus. The clonal deletion is a major mechanism of cell selection and mainly depends on apoptosis. Recently, Itoh et al. isolated cDNAs encoding Fas antigen which mediate apoptosis and is expressed on mouse thymocytes. Herein, I further attempted to examine the expression of Fas antigen gene in human thymocytes from thymus resected at cardiac operations. Human thymocytes were separated into 5 fractions with discontinuous gradient using bovine serum albumin (BSA). They consisted of fractions I (BSA concentrations: 10-14%), II (14-16%), III (16-18%), IV (18-20%), and V (20-24%). Human thymocytes in each fraction were characterized regarding the rearrangement of T cell receptor (TCR) genes and the expression of human Fas antigen gene. Human thymocytes were divided into three sub populations according to their stages of differentiation and maturation. First population, thymocytes contained in fraction I, expressed interleukin 2 receptor alpha-chain (IL-2R alpha) and proliferated without the presence of recombinant IL-2 (rIL-2). Second, thymocytes contained in fraction II and III, expressed IL-2R alpha but could not proliferate without the presence of rIL-2. Third, thymocytes contained in fraction IV and V, could not express IL-2R alpha nor proliferate under any conditions assayed, and occupied over 90% of total human thymocytes in number. The southern blot analysis of T cell receptor beta-chain gene constant region (C beta) showed that C beta were rearranged in most of all thymocytes except for small population contained in fraction I. The reverse transcription-polymerase chain reaction (RT-PCR) analysis of Fas antigen gene expression revealed that the thymocytes in fraction I expressed Fas antigen gene more than those in any other fractions and that the thymocytes in fraction V expressed no Fas antigen gene. These results suggested that Fas antigen plays a minor role in the clonal deletion of postnatal human thymocytes.

Animals↗
PubMed1997

Detection of low-fraction K-ras mutations in primary lung tumors using a sensitive method.

Mutations in the K-ras gene are often identified in lung tumors and are implicated in the development of lung cancer. We used a sensitive method to analyze low-fraction mutations occurring in codon 12 of the K-ras gene in 114 primary lung tumors, including 77 adenocarcinomas, 31 squamous cell carcinomas and 6 adenosquamous carcinomas, which had previously been shown to be negative for codon 12 K-ras mutation in a first screening using less sensitive methods. Sixteen of these tumors were found to contain a low-fraction mutation, including 9 mutations among the adenocarcinomas, six mutations among the squamous cell carcinomas and one mutation among the adenosquamous carcinomas. Our study also showed that the occurrence of low-fraction mutation was associated with a positive smoking history, as was previously found for the occurrence of high-fraction mutation. Patients with low-fraction mutations were younger (mean age 58.8 years) than those with either high-fraction mutations (63.2 years) or no mutation (66 years). Patients with low-fraction mutations were more often stage 1 (8 of 10) than patients with either high fraction mutations (22 of 44) or no mutation (33 of 71). Moreover, the overall survival was better for the group with a low-fraction mutation than both the high-fraction mutation group and the group with no K-ras mutation, but due to small sample size, the difference was not statistically significant. Our results suggest that using highly sensitive methods of K-ras mutant detection in tumor DNA could obscure differences between patients in whom the mutation is found throughout the tumor, those in whom the mutation is only present in a small subpopulation and those who have no mutation.

Adenocarcinoma↗
PubMed1980

Left ventricular ejection fraction changes during recovery from treadmill exercise: a preliminary report of a new method for detecting coronary artery disease.

To test the value of combining treadmill exercise with radionuclide angiography for detecting exercise-induced left ventricular dysfunction, ejection fractions were calculated at rest, peak supine bicycle exercise, and during three supine post-treadmill recovery periods (2-4 min, recovery 1;4-6 min, recovery 2;8-10 min, recovery 3) in ten coronary artery disease patients and eight normal subjects. Both the normal subjects and coronary artery disease patients had normal resting ejection fractions (greater than 0.50). In the normal subjects the mean ejection fraction increased significantly (p less than 0.005) from rest (0.61 +/- 0.03) to peak supine bicycle exercise (0.71 +/- 0.04), and the mean ejection fraction also remained significantly higher (p less than 0.005) at rest than during 10 min post-treadmill exercise. However, the coronary artery disease patients did not significantly change the mean ejection fractions from rest (0.59 +/- 0.06) to peak supine bicycle exercise (0.55 +/- 0.08), and the average ejection fraction during each one of the post-treadmill recovery periods was not significantly different from rest. At the third recovery period all the normals but no coronary artery disease patients had higher ejection fraction than the resting ejection fraction. We thus conclude that the magnitude of change in ejection fraction from rest to 8-10 min post-treadmill exercise in patients with normal resting ejection fraction may be helpful in identifying those with coronary disease.

Angiocardiography↗
PubMed1975

[Some new results from isolation and fractionation of low molecular weight wheat proteins].

The alcohol-soluble wheat gluten fraction (gliadine) and the petroleum-ether-soluble wheat protein fraction (purothionine) were isolated and analysed. The gliadine fraction was itself fractionated by gel chromatography (Sephadex G-100). The partial hydrolysis of sub-fractions (molecular weight 20000-30000) yielded (after separation by gel and ion-exchange chromatography) several peptide fractions. The amino-acid composition and the N- and C-terminal groups of the gliadine fractions were determined. Characteristic differences were stated between various fractions. By means of gel chromatography, purothionine was separated into 4-6 fractions. The study of the amino-acid composition and of the N-terminal groups of the fractions revealed differences in both properties.

Amino Acids↗
PubMed2004

Critical illness myopathy serum fractions affect membrane excitability and intracellular calcium release in mammalian skeletal muscle.

The pathogenesis of myopathies occurring in critically ill patients (critical illness myopathy, CIM) is poorly understood. Both local and systemic responses to sepsis and other severe insults to the body are presumed to be involved but the precise mechanisms by which muscle function is impaired are far from clear. To elucidate such mechanisms we investigated the effects of blood serum fractions (5 kDa to 100 kDa molecular weight cut-off, MWCO) from patients with CIM and from control persons on membrane and contractile functions in intact mammalian single skeletal muscle fibres and chemically skinned fibre bundles. In intact fibres, resting membrane potentials were less negative when exposed to CIM serum fractions compared with control serum fractions. Half-width and maximum rise time of action potentials (AP) were smaller in CIM serum low MWCO fractions vs. control serum. Peak amplitudes of fast inward sodium currents (I(Na)) were increased by low MWCO-CIM fractions compared with control sera fractions. Additionally, voltage dependent inactivation of I(Na) was shifted towards more positive potentials by high MWCO fractions of CIM sera. In skinned fibres, pCa-force relations were similar in CIM and control serum fractions but peak force of Ca2+ induced force transients was decreased by low MWCO-CIM vs. control serum fractions. Our results (i) provide the first evidence that serum from CIM patients affects membrane excitability and the excitation-contraction coupling process at the level of the sarcoplasmic reticulum Ca2+ release of mammalian muscle fibres and (ii) also show that even control serum fractions "per se" alter the response to important physiological membrane and contractility parameters compared with physiological saline.

Animals↗
PubMed1985

Effect of end-diastolic volume on the canine left ventricular ejection fraction.

Left ventricular ejection fraction is commonly used in the clinical assessment of ventricular function. However, the effect of changes in end-diastolic volume on ejection fraction is controversial. The present study examines the effect of changes in end-diastolic volume on ejection fraction in 26 anesthetized dogs on right heart bypass with controlled hemodynamics. At the end of each experiment, pressure-volume relationships were obtained in the potassium arrested heart following suturing of the mitral valve leaflets and clamping of the aortic root. This technique allowed determination of the end-diastolic volume from the end-diastolic pressure. Ejection fraction is highly dependent on end-diastolic volume and end-diastolic pressure at lower levels of end-diastolic volume and end-diastolic pressure. Ejection fraction increased from 30 +/- 1% (SEM) to 64 +/- 2% (p less than 0.001) when end-diastolic pressure was increased from 4 +/- 0.5 to 11 +/- 0.5 cm H2O. The corresponding end-diastolic volumes were 22 +/- 0.5 and 38 +/- 1 ml, respectively (p less than 0.01). Ejection fraction only increased from 64 +/- 2% to 71 +/- 1% (p less than 0.01) when end-diastolic pressure was increased from 11 +/- 0.5 to 18 +/- 1 cm H2O. The corresponding end-diastolic volumes were 38 +/- 1 and 50 +/- 1 ml (p less than 0.01), respectively. This dependence of ejection fraction on preload is present over a wide range of levels of aortic pressure. Similar directional changes in ejection fraction with preload were present after an adequate autonomic blockade, in the presence of either increased or decreased inotropic state and in the presence of an open or closed pericardium. Thus, the present study demonstrates that ejection fraction can be substantially altered by acute changes in end-diastolic volume. This factor should be taken into account when using ejection fraction for the clinical assessment of ventricular function.

Animals↗
PubMed1979

Multiple gated cardiac blood pool imaging for left ventricular ejection fraction: validation of the technique and assessment of variability.

The intrinsic variability and accuracy of left ventricular ejection fraction determined by multiple gated cardiac blood pool imaging was evaluated in 83 patients. Ejection fraction by gated studies correlated well with data from first pass radionuclide angiocardiography (r = 0.94) and from contrast angiography (r = 0.84). Intra- and interobserver variabilities of absolute ejection fraction were minimal (mean +/- standard deviation 1.4 +/- 1.2 and 1.6 +/- 1.5 percent, respectively) and were not different for normal (ejection fraction 55 percent or greater) and abnormal patients. Ejection fraction was determined twice in 70 patients: on the same day at intervals separated by 1 to 2 hours (41 patients) and on 2 different days (29 patients). Ejection fraction ranged from 18 to 91 percent and was normal in 37 patients. There was no difference in mean serial variabilities of absolute ejection fraction for all repeat studies performed on the same and separate days (3.3 +/- 3.1 versus 4.3 +/- 3.1 percent (not significantly different). The mean variability of absolute ejection fraction for repeat studies in normal patients was significantly greater than in abnormal patients (5.4 +/- 4.4 versus 2.1 +/- 2.0 percent, P less than 0.01). The incidence rate of absolute interstudy changes of 5 percent or more was significantly higher in normal than in abnormal patients (P less than 0.01). This differential variability should be considered in interpreting sequential changes in left ventricular ejection fraction. To be attributed to nonrandom physiologic alterations, the absolute change in ejection fraction should be 10 percent or more in normal patients and 5 percent or more in abnormal patients.

Angiocardiography↗
PubMed1993

Characterization of protein kinase C activities in postsynaptic density fractions prepared from cerebral cortex, hippocampus, and cerebellum.

Protein kinase C (PKC) activities, especially, substrates and PKC isozymes, associated with postsynaptic density (PSD) fractions isolated from rat cerebral cortex, hippocampus, or cerebellum were investigated. The 17k M(r) major substrate for PKC was associated with PSD fractions prepared from cerebral cortex and hippocampus, and several substrates including 18k M(r) protein were associated with PSD fraction isolated from cerebellum. The content of 17k M(r) substrate was extremely low in the PSD fraction prepared from cerebellum. PKCs-beta and gamma were associated with PSD fractions and PKC-alpha was virtually absent in the fraction prepared from the three different regions of the brain. All of PKCs-alpha, beta, and gamma were associated with synaptosome fractions. The 36k M(r) bands immunoreactive with anti-PKC-beta antibody, probably degradation products of native PKC-beta, were detected in both the PSD and synaptosome fractions from the three regions, and the ratio of the degradation fragments to native PKC molecule was higher in PSD fractions than in synaptosome fractions. The results suggest postsynaptic roles of PKCs-beta and gamma and involvement of proteolytic activation of PKC-beta in the postsynaptic signal processing.

Amino Acid Sequence↗
PubMed1988

Biological properties of Trimeresurus purpureomaculatus (shore pit viper) venom and its fractions.

The toxic and biological activities of four samples of Trimeresurus purpureomaculatus venom were examined. The lethality, protein composition and biological activities of the four venom samples were similar. Three of the venom samples had LD50 (i.v.) values of 0.9 micrograms/g while the fourth had a lower LD50 (i.v.) of 0.45 micrograms/g. All four venom samples exhibited hemorrhagic, edema-inducing, anticoagulant and thrombin-like activities as well as the usual enzymes found in crotalid venoms. DEAE-Sephacel ion exchange chromatographic fractionation of the venom yielded 10 protein fractions. Only two fractions (fractions A and F) were lethal to mice; the major lethal fraction being fraction F. This fraction had an LD50 (i.v.) of 0.2 micrograms/g and exhibited hemorrhagic, edema-inducing and thrombin-like activity. It also exhibited phospholipase A, arginine ester hydrolase, arginine amidase, protease, 5'-nucleotidase, acetylcholinesterase and alkaline phosphomonoesterase activities. The lethal potency of fraction F is potentiated by fraction G, which exhibited anticoagulant activity as well as hemorrhagic, edema-inducing and enzymatic activities. Fractions F plus G account for almost 100% of the lethal potency of the venom.

Animals↗
PubMed1989

Antigenic relationships of fractionated western diamondback rattlesnake (Crotalus atrox) hemorrhagic toxins and other rattlesnake venoms as indicated by monoclonal antibodies.

Seven hemorrhagic factors have been isolated from Crotalus atrox venom, but their antigenic relationships have not been well studied. In this study, two different monoclonal antibodies, C. atrox peak 8 (CA-P-8) and C. atrox subclone 5 (CA-5+), were produced against two C. atrox venom hemorrhagic fractions and used in an ELISA (enzyme-linked immunosorbent assay) to determine if the hemorrhagic factors in C. atrox venom are antigenically related. The same ELISA test was used to determine cross-reactivity of seven other crude Crotalidae venoms. The two monoclonal antibodies were tested for their ability to neutralize each hemorrhagic HPLC fraction separated from C. atrox venom. C. atrox venom was fractionated into 22 fractions using HPLC analytical DEAE ion exchange. Fractions 4-17 were hemorrhagic. The CA-P-8 monoclonal antibody reacted strongly with hemorrhagic fraction 8; CA-5+ had a broader reactivity and reacted with several HPLC hemorrhagic and non-hemorrhagic fractions. Crude venoms of C. adamanteus, C. scutulatus scutulatus and C. viridis lutosus reacted with CA-P-8, while C. viridis lutosus, C. viridis oreganus, C. scutulatus scutulatus and C. horridus horridus reacted with CA-5+. C. molossus molossus and C. lepidus lepidus did not react with CA-P-8 and CA-5+. Hemorrhagic HPLC fractions 6, 7, 8, were completely neutralized by monoclonal antibody CA-P-8; fraction 9 was partially neutralized. The present study indicated that some C. atrox venom HPLC hemorrhagic fractions have both common and unique epitopes. Antigenic determinants were also found to be shared among different Crotalus species.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Radiation-induced brachial plexus injury: follow-up of two different fractionation schedules.

All 449 breast cancer patients treated with post-operative radiotherapy to the breast and lymph nodes between 1982 and 1984 have been followed for 3-5.5 years. In this group two different fractionation schedules were used, one five times a fortnight and one daily, both over 6 weeks. The calculated dose to the brachial plexus was 45 Gy in 15 fractions or 54 Gy in 30 fractions. These schedules are equivalent doses using the standard NSD formula. The diagnosis of a brachial plexus injury was made clinically and computed tomography was used to distinguish radiation injury from recurrent disease. The actuarial incidence of a radiation-induced brachial plexus injury for the whole group was 4.9% at 5.5 years. No cases were seen in the first 10 months following radiotherapy. The incidence rises between 1 and 4 years and then starts to plateau. When the large fraction size group is compared with the small fraction size group the incidence at 5.5 years is 5.9% and 1.0%, respectively (p = 0.09). Two different treatment techniques were used in this group but were not found to contribute to the probability of developing a brachial plexus injury. It is suggested that radiation using large doses per fraction are less well tolerated by the brachial plexus than small doses per fraction; a commonly used fractionation schedule such as 45 Gy in 15 fractions may give unacceptably high brachial plexus morbidity; and the use of small doses per fraction or avoiding lymphatic irradiation is advocated.

Brachial Plexus↗
PubMed1990

Radiobiological aspects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation.

The biological effects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation in interstitial and intracavitary radiotherapy and total body irradiation are discussed in terms of dose-rate fractionation sensitivity for various tissues. A scaling between dose rate and fraction size was established for acute and late normal-tissue effects which can serve as a guideline for local treatment in the range of dose rates between 0.02 and 0.005 Gy/min and fraction sizes between 8.5 and 2.5 Gy. This is valid provided cell-cycle progression and proliferation can be ignored. Assuming that the acute and late tissue responses are characterised by alpha/beta values of about 10 and 3 Gy and a mono-exponential repair half-time of about 3 h, the same total doses given with either of the two methods are approximately equivalent. The equivalence for acute and late non-hemopoietic normal tissue damage is 0.02 Gy/min and 8.5 Gy per fraction; 0.01 Gy/min and 5.5 Gy per fraction; and 0.005 Gy/min and 2.5 Gy per fraction. A very low dose rate, below 0.005 Gy/min, is thus necessary to simulate high dose-rate radiotherapy with fraction sizes of about 2 Gy. The scaling factor is, however, dependent on the repair half-time of the tissue. A review of published data on dose-rate effects for normal-tissue response showed a significantly stronger dose-rate dependence for late than for acute effects below 0.02 Gy/min. There was no significant difference in dose-rate dependence between various acute non-hemopoietic effects or between various late effects. The consistent dose-rate dependence, which justifies the use of a general scaling factor between fraction size and dose rate, contrasts with the wide range of values for repair half-time calculated for various normal-tissue effects. This indicates that the model currently used for repair kinetics is not satisfactory. There are also few experimental data in the clinical dose-rate range, below 0.02 Gy/min. It is therefore necessary to verify further the presented scaling between fraction size and dose rate.

Animals↗
PubMed1994

Radiotherapy of the rhabdomyosarcoma R1H of the rat: influence of the time interval between two daily fractions during hyperfractionated radiotherapy.

The response of the rhabdomyosarcoma R1H of the rat to hyperfractionated irradiation with different time intervals between the two daily fractions has been investigated. All tumours were exposed to irradiation 5 days per week over 6 weeks. A standard treatment of 30 fractions, i.e. one fraction per day, of 1.83-2.75 Gy (200 kVp X-rays) was compared with a hyperfractionated schedule of 60 fractions, i.e. two fractions per day, of 0.92-1.38 Gy with time intervals of either 1, 2, 3, 5 or 6 h between the two daily fractions. Tumour response has been assessed by (a) net growth delay and (b) local tumour control. Compared with standard treatment (one fraction per day) significant reduction (p < 0.005) of net growth delay was observed for the tumours treated with two daily fractions separated by 2 h. However, at a time interval of 5 and 6 h between the two daily fractions net growth delay increased considerably (p < 0.0001 and p < 0.01) as compared with the standard treatment and an increased rate of local tumour control was observed. The major findings is that tumour response is not as would be predicted by repair if the interval between the two daily fractions exceeds 2 h. The competing or overriding mechanisms cannot be identified ultimately, but the data, though based on small animal numbers and collected over an extended time period, reflect a significant effect.

Animals↗
PubMed1995

The EORTC randomized trial on three fractions per day and misonidazole (trial no. 22811) in advanced head and neck cancer: long-term results and side effects.

From 1981 to 1984, a randomized study was done by the EORTC Radiotherapy Group comparing a fractionation schedule with three fractions per day (multiple fractions per day, MFD), with or without misonidazole, to conventional fractionation. The aim of the study was to obtain improved local and regional control and survival by shortening of the treatment time in the first 2 weeks of irradiation. Three fractions of 1.6 Gy/day (4-h interval) were given during 10 irradiation days to a total of 48 Gy. After 3-4-weeks interval, a boost was given to 67.2 or 72 Gy also in three fractions per day. This schedule was compared to an identical arm with misonidazole 1 g/m2/day and a third arm with conventional fractionation (70 Gy in 35 fractions, 7 weeks or 75 Gy in 44 fractions, 9 weeks). A total number of 523 patients was included in the study. Acute mucositis was much heavier in patients treated with three fractions per day (Van den Bogaert et al. Int. J. Radiat. Oncol. Biol. Phys. 8: 1649-1655, 1982). Early results, communicated in 1986 (Van den Bogaert et al. Int. J. Radiat. Oncol. Biol. Phys. 12: 587-591, 1986) showed no differences in treatment outcome between the three treatment arms. Long-term results and data on late effects are now available. Survival at 5 years was 18% (SE 1.9%) and locoregional control was 27% (SE 2.9%). No statistically significant differences could be observed between the three treatment arms.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗